The goal of this project is to develop a multifunctional and multiplexed nanoparticle-based drug delivery system in order to optimize the targeted delivery and controlled release of vaccine in cancer therapy. To achieve this, we intend to functionalize the surface of our recently developed iron oxide nanoparticles with strong nucleophilic amino groups, thus allowing the attachment of multiple copies of identical tumor antigens. Since the nanoparticles have strong magnetic susceptibility, they will provide microanatomical and functional imaging feedback of the delivery and its effect in cancer therapy using magnetic resonance imaging (MRI). Preliminary data indicate that (i) dextran-coated iron oxide nanoparticles are suitable for in vivo tracking of cell migration using MRI; (ii) the method developed and employed in our laboratory enables the tracking of a small number of cells in the lymph nodes; (iii) the novel epoxide amine linker we developed can functionalize dextran-coated iron oxide nanoparticles with amines on the surface. In this proposal, we hypothesize that the multivalency afforded by the aminated iron oxide nanoparticles can serve as a platform for cancer therapy. The tumor antigen-laden nanoparticles will be formulated as an aerosol and distributed to the lungs via inhalation to induce antitumor immunity. These efforts will be pursued to seek answers to the fundamental questions in cell- based therapy such as (i) given the abundance of dendritic cells in the lungs, will this tissue be a suitable destination at which o activate resident DCs and (ii) does the distribution of tumor antigens via inhalation induce sufficient tumor-specific immunotherapy? We will test our hypothesis by pursuing the following specific aims: (1) Functionalize iron nanoparticles with amines and conjugate the tumor antigens on the surface, and formulate the antigen-iron nanoparticles as an aerosol; (2): Develop MRI techniques to assess the distribution of magnetosol vaccine in the lungs using ultra-short spin echo time. Finally, we will test the efficacy of tumor antigen-nanoparticle magnetosol vaccine on tumor-bearing mice and assess tumor response. PUBLIC HEALTH RELEVANCE: This project describes the development of integrated nanotechnology-based platforms for multifunctional and multiplexed vaccine delivery system in cancer. The iron oxide nanoparticles will be derivatized with tumor antigens and distributed to the lungs as aerosol. Magnetic resonance imaging will be used to track the delivery.